The present invention relates to novel piperazine derivatives, to processes for preparing the novel piperazine derivatives, to novel intermediates useful in the process, to pharmaceutical compositions comprising piperazine derivatives, and to the use of piperazine derivatives in the treatment of disorders of the central nervous system.
It has been disclosed in the scientific literature that certain disorders of the central nervous system may be treated using a modulator of sigma receptor function. Amongst compounds known to possess affinity for sigma ligands are certain piperazine derivatives.
WO 91/09594 discloses compounds having affinity for sigma receptors, certain of which are piperazine derivatives, and discloses that they are useful in the treatment of schizophrenia and other psychoses.
U.S. Pat. No. 5,736,546 discloses certain 1,4-(diphenylalkyl)piperazines having one phenyl group unsubstituted and the other phenyl group substituted by two alkoxy groups. One of the compounds disclosed is 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine. It is also referred to in the scientific literature as SA 4503. The compounds of U.S. Pat. No. 5,736,546 are said to be useful in the treatment of dementia, depression, schizophrenia, anxiety neurosis, diseases accompanying abnormal immune response, cryptorrhea and digestive ulcer.
WO 2004/110387 discloses that sigma ligands, in particular SA 4503, are also useful in the treatment of patients to facilitate neuronal regeneration after onset of a neurodegenerative disease, such as ischemic stroke, traumatic brain injury, or spinal chord injury.
Many 1,4-(diphenylalkyl)piperazines have been disclosed, generically or specifically, although mostly not as sigma ligands. For example, U.S. Pat. No. 5,389,630 generically discloses that certain diamine compounds possess cerebral protective action. The compound 1-[2-(3,4,5-trimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine is commercially available, but is not believed to have any known pharmaceutical use.
It has now been found that certain 1,4-(diphenylalkyl)piperazines, including the known compound 1-[2-(3,4,5-trimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine, have high affinity for sigma receptors, in particular sigma-1 receptors.